DRUG ABUSE AND AIDS--AN IN VITRO IMMUNOLOGICAL MODEL

因为阿片剂和其他滥用药物已经被证明有 免疫调节特性，药物滥用与艾滋病的关联 由此产生的问题是，滥用药物是否可以作为直接的合作伙伴 影响艾滋病发展的因素。最近的证据表明， 这种协同因素的介入要想发泄出来，它的结果必须是 滥用药物与整个神经免疫网络的相互作用。 也就是说，通过影响免疫系统细胞的功能 直接以及通过间接诱导免疫调节 神经、内分泌和免疫系统内的产品。自.以来 这种直接和间接影响的复杂性是无法剖析的。 在实验上，仅通过体内研究，我们就采取了体外实验， 以简化论的方法对这些影响进行建模，并穿透其 很复杂。这种方法的中心是这样一个假设： 滥用药物的免疫调节作用是中介的，主要是， 通过这些药物及其诱导产物与 免疫系统细胞上的表面受体。因此，我们有 靶向受体调节是我们研究的重点，限制了这些 努力研究T细胞，因为已知T细胞受 滥用药物以及作为特定细胞的主要效应者- HIV-1的介导性免疫及其感染性的主要成分 以及艾滋病的发病机制。利用对调节敏感的生物测定 滥用药物及其诱导产物对T细胞受体表达的影响 同时进行电生理和生化评估 这种调制的后果，我们打算调查其性质， 这种调节的程度和药理特异性。信息 然后将被用来表征药物对T细胞的影响。 细胞增殖与运输、归巢和黏附特性的关系 因为这些免疫学属性已知会受到影响 在体内被滥用药物。此外，我们还将描述 滥用药物对HIV-1结合能力的受体调节， 并在T细胞中复制。这些方法加在一起应该提供 需要关于滥用药物作为辅助因素的参与情况的信息 在艾滋病方面。

Since opiates and other drugs of abuse have been shown to have immunomodulatory properties, the association of drug abuse with AIDS has engendered the question of whether drugs of abuse serve as direct co- factors in the development of AIDS. Recent evidence suggests that for such co-factor involvement to transpire, it must happen as the result of the interaction of drugs of abuse with the entire neuroimmune network. That is, by influencing the function of cells of the immune system directly as well as through the indirect induction of immunomodulatory products within the neural, endocrine and immune systems. Since the complexities of such direct and indirect effects cannot be dissected experimentally through in vivo studies alone, we have taken an in vitro, reductionistic approach to model these effects and penetrate their complexities. This approach centers around the hypothesis that the immunomodifying effects of drugs of abuse are mediated, primarily, through interaction of these drugs and their inducted-products with surface receptors on cells of the immune system. Accordingly, we have targeted receptor modulation as the focus of our studies, limiting these efforts to the study of T-cells since they are known to be modulated by drugs of abuse as well as being the primary effectors of specific cell- mediated immunity and principle components in the infectivity of HIV-1 and the pathogenesis of AIDS. Using bioassay sensitive to modulation of T-cell receptor expression by drugs of abuse and their inducted-products, along with electrophysiological and biochemical assessments of the consequences of this modulation, we intend to investigate the nature, extent, and pharmacological specificity of this modulation. Information from such studies will then be used to characterize drug effects on T- cell proliferation and on the trafficking, homing and adhesion properties of T-cells since these immunological attributes are known to be affected in vivo by drugs of abuse. Also, we will characterize the effects of receptor modulation by drugs of abuse on the ability of HIV-1 to bind to, and replicate in T-cells. Together these approaches should provide needed information about the involvement of drugs of abuse as cofactors in AIDS.